Potassium Carbonate → HCID 67389660, compound

HRID 906856Notes

Reaction equation

HRID 906856 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:7]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])[C:11](=[O:22])[C:10]([C:23]#[N:24])=[C:9]([C:25]([F:29])([F:28])[CH2:26][CH3:27])[CH:8]=2)[O:5][CH:6]=1.[CH2:30]([S:32][C:33]1[CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:38]=1)[CH3:31].C([O-])([O-])=O.[K+].[K+]>COCCOC.CCOCC.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[CH2:13][N:12]1[C:7]([C:4]2[O:5][CH:6]=[C:2]([C:35]3[CH:36]=[C:37]([CH:39]([CH3:41])[CH3:40])[CH:38]=[C:33]([S:32][CH2:30][CH3:31])[CH:34]=3)[CH:3]=2)=[CH:8][C:9]([C:25]([F:29])([F:28])[CH2:26][CH3:27])=[C:10]([C:23]#[N:24])[C:11]1=[O:22]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 67388674HCID 67388674, compoundHCID 67389573HCID 67389573, compound

Product 1

HCID 67389660HCID 67389660, compoundYield 44%

Reagents, catalysts & solvents 4

HCID 53485975CID 53485975CatalystHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-(4-bromo-furan-2-yl)-1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-propyl)-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (75 mg, 160 μmol) and 2-(3-ethylsulfanyl-5-isopropyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (73 mg, 240 μmol) in 1,2-dimethoxyethane (2.0 mL) was added K2CO3 (68 mg, 490 μmol) and H2O (200 μL). Dichloro[1,1′-bis(diphenylphosphino)ferrocene)palladium (II) dichloromethane adduct (11 mg, 15 μmol, ˜9 mol %) was added and the resulting dark mixture was sparged with nitrogen for ˜5 minutes. The reaction vial was sealed with a septum that had been pierced with a needle to allow for pressure release, and immersed in an oil bath heated to 80° C. After 5½ hours stirring at 80° C., heating was discontinued and the reaction was allowed to stir at ambient temperature for 16 hrs. The reaction mixture was then diluted with ether and H2O, the layers were separated, and the aqueous was extracted with ether (3×20 mL). The combined ether layers were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford a dark oil. The crude product was purified by silica gel column chromatography by adsorbing the material onto silica gel from a CH2Cl2 solution, loading the resulting solid onto the column and eluting with a gradient from 0% to 20% ethyl acetate/hexane to afford 1-(2,4-difluoro-benzyl)-4-(1,1-difluoro-propyl)-6-[4-(3-ethylsulfanyl-5-isopropyl-phenyl)-furan-2-yl]-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (40 mg, 44% yield) as a brown foam. 1H-NMR (400 MHz, CDCl3): δ 7.85 (1H, d, J=0.8 Hz), 7.18-7.15 (2H, m), 7.12-7.03 (2H, m), 7.00 (1H, d, J=0.8 Hz), 6.87-6.79 (2H, m), 6.76 (1H, s), 5.56 (2H, s), 2.98 (2H, q, J=7.3 Hz), 2.90 (1H, heptet, J=7.1 Hz), 2.34 (2H, t of q, JH-H=7.6 Hz, JH-F=16.9 Hz), 1.34 (3H, t, J=7.3 Hz), 1.27 (6H, d, J=7.1 Hz), 1.13 (3H, t, J=7.3 Hz).

Workup

  1. customthe resulting dark mixture was sparged with nitrogen for ˜5 minutes
  2. customThe reaction
  3. customvial was sealed with a septum that
  4. customimmersed in an oil bath
  5. temperatureheating
  6. stirringto stir at ambient temperature for 16 hrs
  7. customthe layers were separated
  8. extractionthe aqueous was extracted with ether (3×20 mL)
  9. washThe combined ether layers were washed with brine (20 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customto afford a dark oil
  14. customThe crude product was purified by silica gel column chromatography
  15. washeluting with a gradient from 0% to 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-e2c9caa45636426fb37da641efef5171
Source dataset
uspto-grants-2011_09
Patent number
US08013001B2

Reaction notes

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